Methionine-Restricted Diet to Potentiate The Effects of Radiation Therapy

Radiation therapy (RT) is often given concurrently with systemic chemotherapy in order to
sensitize the cancer cells to radiation and increase local and regional disease control.
However, chemotherapy is often associated with significant toxicity and many patients cannot
tolerate it. As such, exploring alternative approaches to radiosensitization that may be more
tolerable for patients is important. One innovative strategy that has potential to enhance
both the safety and efficacy of SBRT is a methionine-restricted diet (MRD) as an adjunct to
radiation therapy. While normal cells can tolerate some degree of methionine deficiency, the
vast majority of cancer cells are methionine auxotrophs that require dietary intake of
methionine. In the absence of methionine, cancer cells undergo cell cycle arrest and cell
death. Preclinical data suggests that consuming a reduced quantity of methionine sensitizes
cancer cells to radiation therapy and reduces metastasis formation and disease progression in
mice; Phase 1 clinical trials have also demonstrated the safety of the diet with and without
concurrent chemotherapy; however, dietary restriction of methionine has not been tested in
combination with radiation therapy in humans. This protocol will test our hypothesis that a
MRD will be a safe addition to radiation therapy for a variety of human malignancies.

Inclusion Criteria:

- Men and women over age 18

- Any non-skin cancer malignancy to be treated with standard of care, curative-intent,
radiation therapy with an RT course of 6 weeks or less, without concurrently
administered cytotoxic chemotherapy. Patients with oligometastatic disease being
treated with local consolidative radiation therapy are also eligible. Pathologic
confirmation of malignancy is not required if the treating physician(s) agree that
this lesion is highly likely to be malignant and the patient elects to forego biopsy.

- The RT plan must achieve standard normal tissue dose-volume constraints.

- Zubrod Performance status 0-2

- Adequate organ and marrow function (leukocytes ≥ 2,000/μL, platelets ≥ 50,000/μL,
hemoglobin > 8.0 g/dL, total bilirubin ≤ 3 X ULN, AST(SGOT)/ALT(SPGT) ≤ 3 X ULN,
albumin > 2.0 g/dL, calcium < 10.5 mg/dL, creatinine ≤ 3 X ULN)

- Negative serum or urine pregnancy test within 72 hours prior to registration for women
of childbearing potential

- Women of childbearing potential and male participants must agree to use a medically
effective means of birth control, such as condom/diaphragm and spermicidal foam,
intrauterine device (IUD), or prescription birth control pills, throughout their
participation in the treatment phase of the study.

- Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

- Prior radiation therapy that would result in overlap of radiation fields.

- Unintentional weight loss of >10% of normal body weight over a period of 6 months or
less.

- Use of an appetite stimulant in the past 6 months for unintentional weight loss.

- Allergy to soy (an ingredient in both methionine-free medical food supplements).

- Administration of cytotoxic chemotherapy within 4 weeks prior to initiation of the
study treatment.

- Use of ongoing biologic/targeted/immune/hormonal therapy will be permitted.

- There should be no intention for the patient to receive other local therapy
(radiotherapy and/or surgery) or cytotoxic chemotherapy within 4 weeks after
completion of the study treatment

- Active systemic, pulmonary, or pericardial infection.

- Psychiatric illness/social situations that would limit compliance with study
requirements. * - Pregnant or lactating women, as treatment involves unforeseeable
risks to the embryo or fetus